Preoperative SRS/SRT vs Postoperative SRS/SRT for Brain Metastases

Inclusion Criteria:

* Patients with prior histopathological diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies.
* MR imaging of the brain with findings strongly suggestive of metastatic tumor(s) as assessed by the radiologist.
* Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate both surgery and SRS/SRT, e.g., the ability to lie flat in a stereotactic soft head frame.
* ECOG ≤ 2
* 1-2 index lesion(s) appropriate for resection, not previously treated with SRS/SRT.

Index lesion(s) should be \> 2 cm and \< 5 cm in largest dimension, and require resection. Alternatively, patients with a diagnosis of melanoma and a lesion \< 1.5cm in largest dimension may also be included. o All other brain lesions must be appropriate for SRS/SRT alone and treated according to physician preference. Prior neurosurgery and/or prior SRS/SRT at a non-overlapping location are permitted at the discretion of the treating physician.

\- MRI confirmed 1-10 lesions, 1-2 of which are the index lesions undergoing surgery.

Each non-index lesion (up to 10) must measure ≤ 3.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection.

* Clinical indication and plan for stereotactic radiosurgery to all known brain lesions requiring treatment (≤ 10 metastases).
* Surgical resection able to be performed within 15 days of radiotherapy completion.
* Written informed consent obtained from subject, or a legally designated power of attorney and ability for subject to comply with the requirements of the study.
* Negative pregnancy test in women of childbearing potential (WOCBP) within 30 days of radiation. WOCBP is a female patient less than 50 years of age or who has menstruated within the last 12 months.
* Platelet count \> 80 k/cumm, Hgb \> 7.5 gm/dL, INR \< 1.3, ANC \> 1.5 k/cumm

Exclusion Criteria:

* Not a surgical candidate per neurosurgeon's discretion.
* Contraindication to general anesthesia.
* Not a radiosurgical candidate per radiation oncologist's discretion.
* Metastatic germ cell tumor, small cell carcinoma, leukemia, multiple myeloma or lymphoma or any primary brain tumor
* ECOG \> 2
* \< 3 months expected survival
* Radiologic documentation of hydrocephalus in addition to symptoms of hydrocephalus
* Radiographic or cytologic evidence of leptomeningeal disease.
* Imaging Findings:

  * Midline shift \> 6mm
  * \>10 lesions, one of which is the index lesion
  * Largest lesion \> 5cm
* Pregnancy
* Known allergy to gadolinium, pacemaker, or other contraindication such as metal implant that is not safe for MRI. Patients with MRI-compatible implants are eligible.
* Patients who have local recurrence of previously treated brain metastasis.
* Patients who have received prior WBRT.
* Inherited radiation hypersensitivity syndromes

  o Ataxia Telangiectasia, Nijmegen Breakage Syndrome, Fanconi Anemia, DNA Ligase IV, Mre 11 deficiency, SCID, Bloom's syndrome
* Collagen vascular diseases

  o Active systemic lupus erythematous (SLE), scleroderma, mixed connective tissue disorder, polymyositis or dermatomyositis, CREST Syndrome
* Cytotoxic Chemotherapy within 7 days prior to SRS/SRT.

  o Molecularly targeted therapies, including immune-modulatory drugs, can be given within 7 days of SRS/SRT at the discretion of the treating physician.
* Patients who received anti-VEGF therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection.
* Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.